Noggin Inhibits IL-1β and BMP-2 Expression, and Attenuates Cartilage Degeneration and Subchondral Bone Destruction in Experimental Osteoarthritis
Noggin Inhibits IL-1β and BMP-2 Expression, and Attenuates Cartilage Degeneration and Subchondral Bone Destruction in Experimental Osteoarthritis
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DOI：
10.3390/cells9040927
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发表时间：
2020-04-01
期刊：
影响因子：
6
通讯作者：
Tang, Chih-Hsin
中科院分区：
文献类型：
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作者：
Chien, Szu-Yu;Tsai, Chun-Hao;Tang, Chih-Hsin
骨关节炎（OA）是一种慢性炎症和进行性关节疾病，导致软骨退化和软骨下骨重建。促炎细胞因子白细胞介素1 β（IL-1 β）在OA中大量表达，并在软骨重塑中起着至关重要的作用，尽管其在软骨和软骨下重塑中的软骨细胞活性中的作用仍不清楚。在这项研究中，用IL-1 β刺激软骨形成ATDC 5细胞增加了骨形态发生蛋白2（BMP-2）的水平，促进了关节软骨降解，并增强了结构重塑。实验性OA大鼠模型中软骨下骨小梁区域的免疫组织化学染色和显微计算机断层扫描成像显示，OA疾病促进关节软骨中IL-1 β、BMP-2和基质金属蛋白酶13（MMP-13）的表达水平，并增强软骨下骨重塑。关节内注射Noggin蛋白（一种BMP-2抑制剂）可减轻OA大鼠的软骨下骨重塑和疾病进展。我们还发现IL-1 β通过激活丝裂原活化蛋白激酶（MEK）、细胞外信号调节激酶（ERK）和特异性蛋白1（Sp1）信号通路增加BMP-2的表达。我们得出结论，IL-1 β通过MEK/ERK/Sp1信号通路促进软骨细胞中BMP-2的表达。头蛋白的施用降低了IL-1 β和BMP-2的表达，从而防止软骨退化和OA发展。
Osteoarthritis (OA) is a chronic inflammatory and progressive joint disease that results in cartilage degradation and subchondral bone remodeling. The proinflammatory cytokine interleukin 1 beta (IL-1 beta) is abundantly expressed in OA and plays a crucial role in cartilage remodeling, although its role in the activity of chondrocytes in cartilage and subchondral remodeling remains unclear. In this study, stimulating chondrogenic ATDC5 cells with IL-1 beta increased the levels of bone morphogenetic protein 2 (BMP-2), promoted articular cartilage degradation, and enhanced structural remodeling. Immunohistochemistry staining and microcomputed tomography imaging of the subchondral trabecular bone region in the experimental OA rat model revealed that the OA disease promotes levels of IL-1 beta, BMP-2, and matrix metalloproteinase 13 (MMP-13) expression in the articular cartilage and enhances subchondral bone remodeling. The intra-articular injection of Noggin protein (a BMP-2 inhibitor) attenuated subchondral bone remodeling and disease progression in OA rats. We also found that IL-1 beta increased BMP-2 expression by activating the mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase (ERK), and specificity protein 1 (Sp1) signaling pathways. We conclude that IL-1 beta promotes BMP-2 expression in chondrocytes via the MEK/ERK/Sp1 signaling pathways. The administration of Noggin protein reduces the expression of IL-1 beta and BMP-2, which prevents cartilage degeneration and OA development.